C2

Effects of malnutrition on epithelia-microbe interactions in the intestinal tract of flies and mice

Maintaining the composition of the beneficial intestinal microbiota requires a homeostatic equilibrium between the microbial community and the intestinal epithelium that serves as the regulatory interface with the host. Nutritional stressors such as malnutrition, starvation or caloric restriction are believed to disturb this equilibrium, thus provoking changes in the intestinal microbiota’s composition as well as in the regenerative capacity and immunological homeostasis of the intestinal mucosa. While malnutrition is a major scourge in developing countries, caloric restriction is believed to deploy positive effects on various health-associated parameters including life span. We aim to elucidate the mechanisms underlying this complex tripartite interplay between microbiota, the intestinal epithelium and the environment (nutritional stressors). More precisely, we want to discover how malnutrition and caloric restriction translate into the corresponding host phenotypes and how the microbiota and the intestinal epithelial reaction contribute to this, or how this influences stem cell behavior, the innate immune repertoire, transcriptional programs and lineage decisions in the epithelium. To achieve these goals, we will use mice and Drosophila as highly versatile experimental model metaorganisms to benefit from their overlapping and complementary inherent strengths. We will combine manipulation of the microbiota with concurrent analysis of the intestinal epithelial response, which will be supplemented by the reciprocal experimental design. These studies will be performed under different nutritional regimes (e.g. malnutrition, caloric restriction) to clarify how they affect the reciprocal interplay between microbiota and intestinal epithelium. Manipulation of the microbiota will comprise fecal transfer experiments and the use of gnotobiotic animals, while manipulation of the intestinal epithelium will be focused on system governing immune homeostasis and stem cell activity. For the latter aspect, manipulation of NF-?B- FoxO-, and Upd3(IL6-equivalent)-mediated signaling systems will be of central importance for the proposed research program.

Researchers

Dr. Christine Fink

Postdoctoral Researcher, Associated Junior Researcher
Kiel University Zoological Institute

Dr. Felix Sommer

Postdoctoral Researcher
Kiel University Institute of Clinical Molecular Biology

Publications

2017

Role of CCL20 mediated immune cell recruitment in NF-κB mediated TRAIL resistance of pancreatic cancer.

Geismann C, Grohmann F, Dreher A, Häsler R, Rosenstiel P, Legler K, Hauser C, Egberts J H, Sipos B, Schreiber S, Linkermann A, Hassan Z, Schneider G, Schäfer H, Arlt A (2017); Biochim Biophys Acta., pii:S0167-4889(17)30030-7. doi: 10.1016/j.bbamcr.2017.02.005

2016

Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.

Wang J, Thingholm L B, Skiecevičienė J, Rausch P, Kummen M, Hov J R, Degenhardt F, Heinsen F A, Rühlemann M C, Szymczak S, Holm K, Esko T, Sun J, Pricop-Jeckstadt M, Al-Dury S, Bohov P, Bethune J, Sommer F, Ellinghaus D, Berge R K, Hübenthal M, Koch M, Schwarz K, Rimbach G, Hübbe P, Pan W-H, Sheibani-Tezerji R, Häsler R, Rosenstiel P, D’Amato M, Cloppenborg-Schmidt K, Künzel S, Laudes M, Marschall H U, Lieb W, Nöthlings U, Karlsen T H, Baines J F, Franke A (2016); Nature Genetics. doi: 10.1038/ng.3695

Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease.

Häsler R, Sheibani-Tezerji R, Sinha A, Barann M, Rehman A, Esser D, Aden K, Knecht C, Brandt B, Nikolaus S, Schäuble S, Kaleta C, Franke A, Fretter C, Müller W, Hütt M T, Krawczak M, Schreiber S, Rosenstiel P (2016); Gut, pii: gutjnl-2016-311651. doi: 10.1136/gutjnl-2016-311651

Biophysical and Population Genetic Models Predict the Presence of “Phantom” Stepping Stones Connecting Mid-Atlantic Ridge Vent Ecosystems.

Breusing C, Biastoch A, Drews A, Metaxas A, Jollivet D, Vrijenhoek R C, Bayer T, Melzner F, Sayavedra L, Petersen J M, Dubilier N, Schilhabel M B, Rosenstiel P, Reusch T B (2016); Curr Biol., 26(17):2257-67. doi: 10.1016/j.cub.2016.06.062

Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.

Aden K, Rehman A, Falk-Paulsen M, Secher T, Kuiper J, Tran F, Pfeuffer S, Sheibani-Tezerji R, Breuer A, Luzius A, Jentzsch M, Häsler R, Billmann-Born S, Will O, Lipinski S, Bharti R, Adolph T, Iovanna J L, Kempster S L, Blumberg R S, Schreiber S, Becher B, Chamaillard M, Kaser A, Rosenstiel P (2016); Cell Rep., 16(8):2208-18. doi: 10.1016/j.celrep.2016.07.054

ABSSeq: a new RNA-Seq analysis method based on modelling absolute expression differences.

Yang W, Rosenstiel P C, Schulenburg H (2016); BMC Genomics., 17:541. doi: 10.1186/s12864-016-2848-2

How well do surrogate hosts serve as model systems for understanding pathogenicity.

Fink C, Roeder T (2016); Advances in Environmental Microbiology, 3:3-25. doi: 10.1007/978-3-319-28170-4_1

Intestinal FoxO signaling is required to survive oral infection in Drosophila.

Fink C, Hoffmann J, Knop M, Li Y, Isermann K, Roeder T (2016); Mucosal Immunol., 9:927-936. doi: 10.1038/mi.2015.112

GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens.

Yang W, Dierking K, Rosenstiel P C, Schulenburg H (2016); Zoology, doi: 10.1016/j.zool.2016.05.013

Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung.

Jansen G, Mahrt N, Tueffers L, Barbosa C, Harjes M, Adolph G, Friedrichs A, Krenz-Weinreich A, Rosenstiel P, Schulenburg H (2016); Evol Med Publ Health, doi: 10.1093/emph/eow016

The native microbiome of the nematode Caenorhabditis elegans: Gateway to a new host-microbiome model

Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, Mader S, Petersen C, Kowallik V, Rosenstiel P C, Felix M A, Schulenburg H (2016); BMC Biology, 14:38. doi:10.1186/s12915-016-0258-1

Age-dependent pathogenesis of enteropathogenic Escherichia coli (EPEC) in mice.

Dupont A, Sommer F, Zhang K, Repnik U, Basic M, Bleich A, Kühnel M, Bäckhed, Litvak Y, Fulde M, Rosenshine I, Hornef M W (2016); PLoS Pathog., 12(5):e1005616. doi: 10.1371/journal.ppat.1005616

Know your neighbor: Microbiota and host epithelial cells interact locally to control intestinal function and physiology.

Sommer F, Bäckhed F (2016); Bioessays, 38(5):455-64. doi: 10.1002/bies.201500151

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin.

Kim D, Kim YG, Seo SU, Kim DJ, Kamada N, Prescott D, Philpott DJ, Rosenstiel P, Inohara N, Núñez G (2016); Nat Med, 22:524-530. doi: 10.1038/nm.4075

Genome-wide rare copy number variation screening in ulcerative colitis identifies potential susceptibility loci.

Saadati H R, Wittig M, Helbig I, Häsler R, Anderson C A, Mathew C G, Kupcinskas L, Parkes M, Karlsen T H, Rosenstiel P, Schreiber S, Franke A (2016); BMC Med. Genet.,  doi: 10.1186/s12881-016-0289-z

The gut microbiota modulates energy metabolism in the hibernating brown bear (Ursus arctos).

Sommer F, Ståhlman M, Ilkayeva O, Arnemo J M, Kindberg J, Josefsson J, Newgard C B, Fröbert O, Bäckhed F (2016); Cell Reports, 14(7):1655-1661. doi:10.1016/j.celrep.2016.01.026

Microbiota-induced obesity requires farnesoid X receptor.

Parséus A, Sommer N, Sommer F, Caesar R, Molinaro A, Ståhlman M, Greiner T U, Perkins R, Bäckhed F (2016); Gut microbiota, doi: 10.1136/gutjnl-2015-310283

2015

Abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels.

Sayavedra L, Kleiner M, Ponnudurai R, Wetzel S, Pelletier E, Barbe V, Satoh N, Shoguchi E, Fink D, Breusing C, Reusch T B, Rosenstiel P, Schilhabel M B, Becher D, Schweder T, Markert S, Dubilier N, Petersen J M (2015); Elife, 4:e07966. doi:10.7554/eLife.07966

Expression analysis of octopamine
and tyramine receptors in Drosophila.

El-Kholy S, Stephano F, Li Y, Bhandari A, Fink C, Roeder T (2015); Cell Tissue Res., 361(3):669-684. doi: 10.1007/s00441-015-2137-4

Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator Mutations Mediate Fitness Gains through Virulence Attenuation.

Jansen G, Crummenerl LL, Gilbert F, Mohr T, Pfefferkorn R, Thänert R, Rosenstiel P, Schulenburg H (2015); Mol Biol Evol., 32(11) 2883-2896. doi: 10.1093/molbev/msv160

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin.

Heinsen F A, Knecht H, Neulinger S C, Schmitz R A, Knecht C, Kühbacher T, Rosenstiel P C, Schreiber S, Friedrichs A K, Ott S J (2015); Gut Microbes., 6(4):243-54. doi: 10.1080/19490976.2015.1062959.

Secreted Frizzled-related protein 3 (sFRP3)-mediated suppression of interleukin-6 receptor release by A disintegrin and metalloprotease 17 (ADAM17) is abrogated in the osteoarthritis-associated rare double variant of sFRP3.

Oldefest M, Düsterhöft S, Desel C, Thysen S, Fink C, Rabe B, Lories R, Grötzinger J, Lorenzen I; Biochem J., 468(3):507-18. doi: 10.1042/BJ20141231

Host-pathogen coevolution: the selective
advantage of Bacillus thuringiensis virulence and its Cry toxin genes.

Masri L, Branca A, Sheppard AE, Papkou A, Laehnemann D, Guenther PS, Prahl S, Saebelfeld M,
Hollensteiner J, Liesegang H, Brzuszkiewicz E, Daniel R, Michiels NK, Schulte RD, Kurtz J, Rosenstiel
 P, Telschow A, Bornberg-Bauer E, Schulenburg H (2015); PLoS Biol., doi: 10.1371/journal.pbio.1002169

Site-specific programming of the host epithelial transcriptome by the gut microbiota.

Sommer F, Nookaew I, Sommer N, Fogelstrand P, Bäckhed F (2015); Genome Bio, 16(32). doi: 10.1186/s13059-015-0614-4

The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium.

Sommer F, Bäckhed F (2015); Mucosal Immunol, 8(2):372-379. doi: 10.1038/mi.2014.74

The octopamine receptor octß2R is essential for ovulation and fertilization in the fruit fly Drosophila melanogaster.

Li Y, Fink C, El-Kholy S, Roeder T (2015); Arch Insect Biochem Physiol., 88(3):168-78. doi: 10.1002/arch.21211

Overlapping and unique signatures in the proteomic and transcriptomic responses of the nematode Caenorhabditis elegans towards pathogenic Bacillus thuringiensis.

Yang W, Dierking K, Esser D, Tholey A, Leippe M, Rosenstiel P, Schulenburg H (2015); Dev Comp Immunol, 51:1-9. doi: 10.1016/j.dci.2015.02.010

The composition of the gut microbiota shapes the colon mucus barrier.

Jakobsson H E, Rodríguez-Piñeiro A M, Schütte A, Ermund A, Boysen P, Bemark M, Sommer F, Bäckhed F, Hansson G C, Johansson M E V (2015); EMBO Rep, 16(2):164-77. doi: 10.15252/embr.201439263

Geographical patterns of the standing and active human gut microbiome in health and IBD.

Rehman A, Rausch P, Wang J, Skieceviciene J, Kiudelis G, Bhagalia K, Amarapurkar D, Kupcinskas L, Schreiber S, Rosenstiel P, Baines J F, Ott S (2015); Gut, 65(2):238-248. doi: 10.1136/gutjnl-2014-308341

2014

Whole genome and exome sequencing of monozygotic twins discordant for Crohn’s disease.

Petersen B S, Spehlmann M E, Raedler A, Stade B, Thomsen I, Rabionet R, Rosenstiel P, Schreiber S, Franke A (2014); BMC Genomics, 15(1):564. doi: 10.1186/1471-2164-15-564

Species-specific viromes in the ancestral holobiont Hydra.

Grasis J A, Lachnit T, Anton-Erxleben F, Lim Y W, Schmieder R, Fraune S, Franzenburg S, Insua S, Machado G, Haynes M, Little M, Kimble R, Rosenstiel P, Rohwer F L, Bosch T C (2014); PLoS One., 9(10):e109952. doi: 10.1371/journal.pone.0109952

c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells.

Geismann C, Grohmann F, Sebens S, Wirths G, Dreher A, Häsler R, Rosenstiel P, Hauser C, Egberts J H, Trauzold A, Schneider G, Sipos B, Zeissig S, Schreiber S, Schäfer H, Arlt A (2014); Cell Death Dis., ; 5:e1455. doi: 10.1038/cddis.2014.417

Molekulare Analyse aminerger Signalwege im ZNS der Taufliege.

Fink C, Schukies S, von Frieling J, Roeder T (2014); Biospektrum, 20(6):636-639. doi: 10.1007/s12268-014-0499-x

Transcriptional regionalization of the fruit fly’s airway epithelium.

Faisal M N, Hoffmann J, El-Kholy S, Kallsen K, Wagner C, Bruchhaus I, Fink C, Roeder T (2014);
PLoS One., 9(7):e102534. doi: 10.1371/journal.pone.0102534

Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice.

Wang J, Linnenbrink M, Künzel S, Fernandes R, Nadeau M J, Rosenstiel P, Baines J F (2014); Proc Natl Acad Sci U S A., 111(26):E2703-10. doi: 10.1073/pnas.1402342111

Effects of β-lactam antibiotics and fluoroquinolones on human gut microbiota in relation to Clostridium difficile associated diarrhea.

Knecht H, Neulinger S C, Heinsen F A, Knecht C, Schilhabel A, Schmitz R A, Zimmermann A, dos Santos V M, Ferrer M, Rosenstiel P C, Schreiber S, Friedrichs A K, Ott S J (2014); PLoS One., 9(2):e89417. doi: 10.1371/journal.pone.0089417

XIAP variants in male Crohn’s disease.

Zeissig Y, Petersen B S, Milutinovic S, Bosse E, Mayr G, Peuker K, Hartwig J, Keller A, Kohl M, Laass M W, Billmann-Born S, Brandau H, Feller A C, Röcken C, Schrappe M, Rosenstiel P, Reed J C, Schreiber S, Franke A, Zeissig S (2014); Gut., 64(1):66-76. doi: 10.1136/gutjnl-2013-306520

Regulation of polyp-to-jellyfish transition in Aurelia aurita.

Fuchs B, Wang W, Graspeuntner S, Li Y, Insua S, Herbst E M, Dirksen P, Bohm A M, Hemmrich G, Sommer F, Domazet-Loso T, Klostermeier U C, Anton-Erxleben F, Rosenstiel P, Bosch T C, Khalturin K (2014); Curr Biol, 24(3):263-273. doi: 10.1016/j.cub.2013.12.003

Altered Mucus Glycosylation in Core 1 O-Glycan-Deficient Mice Affects Microbiota Composition and Intestinal Architecture.

Sommer F, Adam N, Johansson M E V, Xia L, Hansson G C, Bäckhed F (2014); PLoS One, 9(1):e85254. doi: 10.1371/journal.pone.0085254

2013

When the most potent combinations of antibiotics select for the greatest bacterial
load: the smile-frown transition.

Peña-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P, Schulenburg H,
 Beardmore R (2013); PLoS Biol., 11:e1001540. doi: 10.1371/journal.pbio.1001540

NOD2-dependent licensing of the microbiota intrinsically prevents
transmissible intestinal inflammation and tumorigenesis in mice.

Couturier A, Secher T, Rehman A, Normand S, Arcangelis A, Haesler R, Huot L, Grandjean T,
Bressenot A, Delanoye A, Gaillot O, Schreiber S, Lemoine Y, Ryffel B, Hot D, Nunez G, Chen G,
 Rosenstiel P, Chamaillard M (2013); J Clin Invest 1, 123(2):700-11. doi: 10.1172/JCI62236

Janus–a comprehensive
tool investigating the two faces of transcription.

Barann M, Esser D, Klostermeier U C, Lappalainen T, Luzius A, Kuiper J W, Ammerpohl O, Vater I,
Siebert R, Amstislavskiy V, Sudbrak R, Lehrach H, Schreiber S, Rosenstiel P (2013); Bioinformatics., 29(13):1600-1606. doi: 10.1093/bioinformatics/btt185

NOD2-mediated dysbiosis predisposes
mice to transmissible colitis and colorectal cancer.

Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Häsler R, Huot L,
Grandjean T, Bressenot A, Delanoye-Crespin A, Gaillot O, Schreiber S, Lemoine Y, Ryffel B, Hot
D, Nùñez G, Chen G, Rosenstiel P, Chamaillard M (2013); J. Clin. Invest., 123(2):700-11. doi: 10.1172/JCI62236

Initial symbiont contact orchestrates host-organ-wide transcriptional changes that
prime tissue colonization.

Kremer N, Philipp E E R, Carpentier M-C, Brennan C A, Kraemer L, Altura M A, Augustin R, Häsler R,
 Heath-Heckman E A C, Peyer S M, Schwartzman J, Rader B A, Ruby E G, Rosenstiel P, McFall-
Ngai M J (2013); Cell Host Microbe, 14(2):183-194. doi: 10.1016/j.chom.2013.07.006

Transcriptome and genome sequencing uncovers
functional variation in humans.

Lappalainen T, Sammeth M, Friedländer M R, ’t Hoen P A C, Monlong J, Rivas M A, Gonzàlez-Porta M,
 Kurbatova N, Griebel T, Ferreira P G, Barann M, Wieland T, Greger L, van Iterson M, Almlöf J, 
Ribeca P, Pulyakhina I, Esser D, Giger T, Tikhonov A, Sultan M, Bertier G, MacArthur D G, Lek M,
 Lizano E, Buermans H P J, Padioleau I, Schwarzmayr T, Karlberg O, Ongen H, Kilpinen H, Beltran 
S, Gut M, Kahlem K, Amstislavskiy V, Stegle O, Pirinen M, Montgomery S B, Donnelly P, McCarthy
 M I, Flicek P, Strom T M, Geuvadis Consortium, Lehrach H, Schreiber S, Sudbrak R, Carracedo A, 
Antonarakis S E, Häsler R, Syvänen A-C, van Ommen G-J, Brazma A, Meitinger T, Rosenstiel P,
Guigó R, Gut I G, Estivill, Dermitzakis E T (2013); Nature., 501(7468):506-511. doi: 10.1038/nature12531

Reproducibility of
high-throughput mRNA and small RNA sequencing across laboratories.

van Ommen G J, Estivill X, Guigó R, Syvänen A C, Gut I G, Dermitzakis E T, Antonarakis S E, Brazma A, Flicek P, Schreiber S, Rosenstiel P, Meitinger T, Strom T M, Lehrach H, Sudbrak R, Carracedo A, ‘t Hoen PA , Pulyakhina I, Anvar S Y, Laros J F, Buermans H P, van Iterson M, Friedländer M R, Monlong J, Lizano E, Bertier G, Ferreira P G, Sammeth M, Almlöf J, Karlberg O, Brännvall M, Ribeca P, Griebel T, Beltran S, Gut M, Kahlem K, Lappalainen T, Giger T, Ongen H, Padioleau I, Kilpinen H, Gonzàlez-Porta M, Kurbatova N, Tikhonov A, Greger L, Barann M, Esser D, Häsler R, Wieland T, Schwarzmayr T, Sultan M, Amstislavskiy V (2013); Nat. Biotechnol., 31(11):1015-22. doi: 10.1038/nbt.2702

The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.

Bochenek G, Häsler R, El Mokhtari N E, König I R, Loos B G, Jepsen S, Rosenstiel P, Schreiber S, Schaefer A S (2013); Hum Mol Genet., 22(22):4516-27. doi: 10.1093/hmg/ddt299

Paneth cells as a site of origin for intestinal inflammation.

Adolph T E, Tomczak M F, Niederreiter L, Ko H J, Böck J, Martinez-Naves E, Glickman JN,
Tschurtschenthaler M, Hartwig J, Hosomi S, Flak M B, Cusick J L, Kohno K, Iwawaki T, Billmann-Born
S, Raine T, Bharti R, Lucius R, Kweon M N, Marciniak S J, Choi A, Hagen S J, Schreiber S, Rosenstiel
 P, Kaser A, Blumberg R S (2013); Nature., 503(7475):272-6. doi: 10.1038/nature12599

Non-invasive analysis of microbiome
 dynamics in the fruit fly Drosophila melanogaster.

Fink C, Staubach F, Kuenzel S, Baines JF, Roeder T (2013); Appl Environ Microbiol., 79(22):6984-6988. doi: 10.1128/AEM.01903-13

Association between variants of PRDM1 and NDP52 and Crohn’s disease, based on exome sequencing and functional studies.

Ellinghaus D, Zhang H, Zeissig S, Lipinski S, Till A, Jiang T, Stade B, Bromberg Y, Ellinghaus E, Keller A, Rivas M A, Skieceviciene J, Doncheva N T, Liu X, Liu Q, Jiang F, Forster M, Mayr G, Albrecht M, Häsler R, Boehm B O, Goodall J, Berzuini C R, Lee J, Andersen V, Vogel U, Kupcinskas L, Kayser M, Krawczak M, Nikolaus S, Weersma R K, Ponsioen C Y, Sans M, Wijmenga C, Strachan D P, McArdle W L, Vermeire S, Rutgeerts P, Sanderson J D, Mathew C G, Vatn M H, Wang J, Nöthen M M, Duerr R H, Büning C, Brand S, Glas J, Winkelmann J, Illig T, Latiano A, Annese V, Halfvarson J, D’Amato M, Daly M J, Nothnagel M, Karlsen T H, Subramani S, Rosenstiel P, Schreiber S, Parkes M, Franke A (2013); Gastroenterology., 145(2):339-47. doi: 10.1053/j.gastro.2013.04.040

Base-pair resolution DNA methylome of the EBV-positive Endemic Burkitt lymphoma cell line DAUDI determined by SOLiD bisulfite-sequencing.

Kreck B, Richter J, Ammerpohl O, Barann M, Esser D, Petersen B S, Vater I, Murga Penas E M, Bormann Chung C A, Seisenberger S, Lee Boyd V, Smallwood S, Drexler H G, Macleod R A, Hummel M, Krueger F, Häsler R, Schreiber S, Rosenstiel P, Franke A, Siebert R (2013); Leukemia., 27(8):1751-3. doi: 10.1038/leu.2013.4

Drosophila as a model to study metabolic disorders.

Hoffmann J1, Romey R, Fink C, Roeder T (2013); Adv Biochem Eng Biotechnol., 135:41-61. doi: 10.1007/10_2013_196

The gut microbiota – masters of host development and physiology.

Sommer F, Bäckhed F (2013);  Nat Rev Microbiol, 11(4):227-238. doi: 10.1038/nrmicro2974

Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

Noth R, Häsler R, Stüber E, Ellrichmann M, Schäfer H, Geismann C, Hampe J, Bewig B, Wedel T, Böttner M, Schreiber S, Rosenstiel P, Arlt A (2013); Am J Physiol Gastrointest Liver Physiol., 304(7):G646-54. doi: 10.1152/ajpgi.00246.2012

Overexpression of Sir2 in the adult fat body
is sufficient to extend lifespan of male and female Drosophila.

Hoffmann J, Romey R, Fink C, Yong L, Roeder T (2013); Aging, 5(4):315-327. doi: 10.18632/aging.100553

Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis.

Arlt A, Bharti R, Ilves I, Häsler R, Miettinen P, Paajanen H, Brunke G, Ellrichmann M, Rehman A, Hauser C, Egberts J H, Ott S J, Schreiber S, Rosenstiel P, Herzig K H (2013); Innate Immun., 21(1):30-41. doi: 10.1177/1753425913515033

2012

RNAi screening identifies mediators of NOD2 signaling: implications for spatial specificity of MDP recognition.

Lipinski S, Grabe N, Jacobs G, Billmann-Born S, Till A, Häsler R, Aden K, Paulsen M, Arlt A, Kraemer L, Hagemann N, Erdmann K S, Schreiber S, Rosenstiel P (2012); Proc Natl Acad Sci U S A., 109(52):21426-31. doi: 10.1073/pnas.1209673109

Ace2 links dietary malnutrition to microbial
ecology and intestinal inflammation.

Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino P, Sigl V, Wild B, Hanada T, Hanada
 R, Lipinski S, Wild B, Camargo S, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers
H, Verrey F, Rosenstiel P, Penninger J M (2012); Nature, 487(7408):477-81. doi: 10.1038/nature11228

Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated
genome, exome and transcriptome sequencing.

The ICGC MMML-Seq Project, Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B,
 Rosolowski M, (…) Lichter P, Eils R, Küppers R, Hummel M, Klapper W, Rosenstiel P, Rosenwald A,
 Brors B, Siebert R (2012); Nature Genet., doi: 10.1038/ng.2469

FoxO is a critical regulator of stem cell maintenance and immortality in Hydra.

Boehm A M, Hemmrich G, Khalturin K, Puchert M, Anton-Erxleben F, Wittlieb J, Klostermeier U C, Rosenstiel P, Oberg H H, Bosch T C G (2012); Proc Natl Acad Sci USA, 109(48):19697-702. doi: 10.1073/pnas.1209714109

A functional methylome map in ulcerative
colitis.

Häsler R, Feng Z, Baeckdahl L, Spehlmann M E, Franke A, Teschendorff A, Rakyan V, Down T, Wilson
G, Feber A, Beck S, Schreiber S, Rosenstiel P (2012); Genome Research, 22(11):2130-7. doi: 10.1101/gr.138347.112

Blood system formation in the urochordate Ciona intestinalis requires the variable receptor vCRL1.

Sommer F, Awazu S, Anton-Erxleben F, Jiang D, Klimovich A V, Klimovich B V, Samoilovich M P, Satou Y, Krüss M, Gelhaus C, Kürn U, Bosch T C, Khalturin K (2012); Mol Biol Evol., 29(10): 3081-3093. doi: 10.1093/molbev/mss120

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.

Folseraas T, Melum E, Rausch P, Juran B D, Ellinghaus E, Shiryaev A, Laerdahl J K, Ellinghaus D, Schramm C, Weismüller T J, Gotthardt D N, Hov J R, Clausen O P, Weersma R K, Janse M, Boberg K M, Björnsson E, Marschall H U, Cleynen I, Rosenstiel P, Holm K, Teufel A, Rust C, Gieger C, Wichmann H E, Bergquist A, Ryu E, Ponsioen C Y, Runz H, Sterneck M, Vermeire S, Beuers U, Wijmenga C, Schrumpf E, Manns M P, Lazaridis K N, Schreiber S, Baines J F, Franke A, Karlsen T H (2012); J Hepatol., 57(2):366-75. doi: 10.1016/j.jhep.2012.03.031

Microbial pattern recognition causes distinct functional micro-RNA signatures in primary human monocytes.

Häsler R, Jacobs G, Till A, Grabe N, Cordes C, Nikolaus S, Lao K, Schreiber S, Rosenstiel P (2012); PLoS One., 7(2):e31151. doi: 10.1371/journal.pone.0031151

2011

Transcriptomic resilience to global warming in the seagrass Zostera marina, a marine
foundation species.

Franssen S U, Gu J, Bergmann N, Winters G, Klostermeier U C, Rosenstiel P, Bornberg-Bauer E, Reusch T B (2011); Proc Natl Acad Sci U S A., 108(48):19276-81. doi: 10.1073/pnas.1107680108

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype

Rausch P, Rehman A, Künzel S, Häsler R, Ott S J, Schreiber S, Rosenstiel P, Franke A, Baines J F (2011); Proc Natl Acad Sci USA, 108 (47): 19030-5. doi: 10.1073/pnas.1106408108

A genome-wide association study reveals evidence of association with sarcoidosis at 6p12.1.

Hofmann S, Fischer A, Till A, Müller-Quernheim J, Häsler R, Franke A, Gäde K I, Schaarschmidt H, Rosenstiel P, Nebel A, Schürmann M, Nothnagel M, Schreiber S; GenPhenReSa Consortium (2011); Eur Respir J., 38(5):1127-35. doi: 10.1183/09031936.00001711

Nod2 is essential
 for temporal development of intestinal microbial communities.

Rehman A, Sina C, Gavrilova O, Häsler R, Ott S, Baines J F, Schreiber S, Rosenstiel P (2011); Gut, 60(10):1354-62. doi: 10.1136/gut.2010.216259

Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model.

Noth R, Lange-Grumfeld J, Stüber E, Kruse ML, Ellrichmann M, Häsler R, Hampe J, Bewig B, Rosenstiel P, Schreiber S, Arlt A (2011); BMC Gastroenterol., 11:109. doi: 10.1186/1471-230X-11-109

Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener’s granulomatosis.

Laudien M1, Häsler R, Wohlers J, Böck J, Lipinski S, Bremer L, Podschun R, Ambrosch P, Lamprecht P, Rosenstiel P, Till A (2011); Mucosal Immunol., 4(5):564-73. doi: 10.1038/mi.2011.9

A tissue-specific landscape of sense/antisense transcription in the mouse intestine.

Klostermeier U C, Barann M, Wittig M, Häsler R, Franke A, Gavrilova O, Kreck B, Sina C, Schilhabel M B, Schreiber S, Rosenstiel P (2011); BMC Genomics., 12:305. doi: 10.1186/1471-2164-12-305

Alterations of pre-mRNA splicing in human inflammatory bowel disease.

Häsler R, Kerick M, Mah N, Hultschig C, Richter G, Bretz F, Sina C, Lehrach H, Nietfeld W, Schreiber S, Rosenstiel P (2011); Eur J Cell Biol., 90(6-7):603-11. doi: 10.1016/j.ejcb.2010.11.010

Maternal epigenetic 
pathways control parental contributions to early embryogenesis.

Autran D, Baroux C, Raissig M, Lenormand G, Wittig M, Grob S, Steimer A, Barann M, Klostermeier U,
 Leblanc O, Vielle-Calzade JP, Rosenstiel P, Grimanelli D, Grossniklaus U (2011); Cell, 145(5):707-19. doi: 10.1016/j.cell.2011.04.014

Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn’s disease-associated NOD2 variant L1007fsinsC.

Billmann-Born S, Till A, Arlt A, Lipinski S, Sina C, Latiano A, Annese V, Häsler R, Kerick M, Manke T, Seegert D, Hanidu A, Schäfer H, van Heel D, Li J, Schreiber S, Rosenstiel P (2011); J Immunol., 186(7):4027-38. doi: 10.4049/jimmunol.1000085

2010

Molecular analysis of self/non-self recognition in the hermaphroditic urochordate Ciona intestinalis.

Sommer F (2010); Ph.D. thesis. University of Kiel. doi: 10.13140/RG.2.1.2498.5126

Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.

Chalaris A, Adam N, Sina C, Rosenstiel P, Lehmann-Koch J, Schirmacher P, Hartmann D, Cichy J, Gavrilova O, Schreiber S, Jostock T, Matthews V, Häsler R, Becker C, Neurath M F, Reiss K, Saftig P, Scheller J, Rose-John S (2010); J Exp Med., 207(8):1617-24. doi: 10.1084/jem.20092366

Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL).

Franke A, Balschun T, Sina C, Ellinghaus D, Häsler R, Mayr G, Albrecht M, Wittig M, Buchert E, Nikolaus S, Gieger C, Wichmann H E, Sventoraityte J, Kupcinskas L, Onnie CM, Gazouli M, Anagnou N P, Strachan D, McArdle W L, Mathew C G, Rutgeerts P, Vermeire S, Vatn M H; IBSEN study group, Krawczak M, Rosenstiel P, Karlsen T H, Schreiber S (2010); Nat Genet., 42(4):292-4. doi: 10.1038/ng.553

The nucleotide-binding oligomerization domain-like receptor NLRC5 is involved in IFN-dependent antiviral immune responses.

Künzel S, Till A, Winkler M, Häsler R, Lipinski S, Jung S, Grötzinger J, Fickenscher H, Schreiber S, Rosenstiel P (2010); J Immunol., 184(4):1990-2000. doi: 10.4049/jimmunol.0900557

Caenopores are antimicrobial
peptides in the nematode Caenorhabditis elegans instrumental in nutrition and immunity.

Roeder T, Stanisak M, Gelhaus C, Bruchhaus I, Grötzinger J, Leippe M (2010); 
Dev Comp Immunol, 34 (2):203-209. doi: 10.1016/j.dci.2009.09.010

2009

Decreased sigmoidal ABCB1 (P-glycoprotein) expression in ulcerative colitis is associated with disease activity.

Ufer M, Häsler R, Jacobs G, Haenisch S, Lächelt S, Faltraco F, Sina C, Rosenstiel P, Nikolaus S, Schreiber S, Cascorbi I (2009); Pharmacogenomics., 10(12):1941-53. doi: 10.2217/pgs.09.128

G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation.

Sina C, Gavrilova O, Förster M, Till A, Derer S, Hildebrand F, Raabe B, Chalaris A, Scheller J, Rehmann A, Franke A, Ott S, Häsler R, Nikolaus S, Fölsch UR, Rose-John S, Jiang HP, Li J, Schreiber S, Rosenstiel P (2009); J Immunol., 183(11):7514-22. doi: 10.4049/jimmunol.0900063

A functional EXO1 promoter variant is associated with prolonged life expectancy in centenarians.

Nebel A, Flachsbart F, Till A, Caliebe A, Blanché H, Arlt A, Häsler R, Jacobs G, Kleindorp R, Franke A, Shen B, Nikolaus S, Krawczak M, Rosenstiel P, Schreiber S (2009); Mech Ageing Dev., 130(10):691-9. doi: 10.1016/j.mad.2009.08.004

Infection induces a survival program and local remodelling in
 the airway epithelium in the fly.

Wagner C, Isermann K, Roeder T (2009); FASEB J, 23(7):2045-2054. doi: 10.1096/fj.08-114223

Genetic control of global gene expression levels in the intestinal mucosa: a human twin study.

Häsler R, Begun A, Freitag-Wolf S, Kerick M, Mah N, Zvirbliene A, Spehlmann M E, von Wurmb-Schwark N, Kupcinskas L, Rosenstiel P, Schreiber S (2009); Physiol Genomics., 38(1):73-9. doi: 10.1152/physiolgenomics.00010.2009

Drosophila in asthma research.

Roeder T, Isermann K, Kabesch M (2009); Am J Res Crit Care Med, 
179(11):979-983. doi: 10.1164/rccm.200811-1777PP

Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence.

Bosch T C, Augustin R, Anton-Erxleben F, Fraune S, Hemmrich G, Zill H, Rosenstiel P, Jacobs G, Schreiber S, Leippe M, Stanisak M, Grötzinger J, Jung S, Podschun R, Bartels J, Harder J, Schröder J M (2009); Dev Comp Immunol., 33(4):559-69. doi: 10.1016/j.dci.2008.10.004

2008

Molecular architecture of the fruit
fly’s airway epithelial immune system.

Wagner C, Isermann K, Fehrenbach H, Roeder T (2008); BMC Genomics, 9:446. doi: 10.1186/1471-2164-9-446

Systematic expression profiling of innate immune genes defines a complex pattern of immunosenescence in peripheral and intestinal leukocytes.

Rosenstiel P, Derer S, Till A, Häsler R, Eberstein H, Bewig B, Nikolaus S, Nebel A, Schreiber S (2008); Genes Immun., 9(2):103-14. doi: 10.1038/sj.gene.6364454

2007

Systematic association mapping identifies NELL1 as a novel IBD disease gene.

Franke A, Hampe J, Rosenstiel P, Becker C, Wagner F, Häsler R, Little R D, Huse K, Ruether A, Balschun T, Wittig M, Elsharawy A, Mayr G, Albrecht M, Prescott N J, Onnie C M, Fournier H, Keith T, Radelof U, Platzer M, Mathew C G, Stoll M, Krawczak M, Nürnberg P, Schreiber S (2007); PLoS One., 2(8):e691. doi: 10.1371/journal.pone.0000691

A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1.

Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega F M, Briggs J, Günther S, Prescott N J, Onnie C M, Häsler R, Sipos B, Fölsch U R, Lengauer T, Platzer M, Mathew C G, Krawczak M, Schreiber S (2007); Nat Genet., 39(2):207-11. doi: 10.1038/ng1954

Allorecognition in urochordates: identification of a highly variable complement receptor-like protein expressed in follicle cells of Ciona.

Kurn U, Sommer F, Hemmrich G, Bosch T C, Khalturin K (2007); Dev Comp Immunol., 31(4):360-371. doi: 10.1016/j.dci.2006.06.008

2006

In the urochordate Ciona intestinalis zona pellucida domain proteins vary among individuals.

Kurn U, Sommer F, Bosch T C, Khalturin K (2006); Developmental and comparative immunology, 31(12): 1242-1254. doi: 10.1016/j.dci.2007.03.011

Fast and simple DNA extraction from saliva and sperm cells obtained from the skin or isolated from swabs.

von Wurmb-Schwark N, Mályusz V, Fremdt H, Fink C, Simeoni E, Schwark T (2006); Leg Med (Tokyo), 8(3):177-81. doi: 10.1016/j.legalmed.2005.11.004

Analysis of NOD2-mediated proteome response to muramyl dipeptide in HEK293 cells.

Weichart D, Gobom J, Klopfleisch S, Häsler R, Gustavsson N, Billmann S, Lehrach H, Seegert D, Schreiber S, Rosenstiel P (2006); J Biol Chem., 281(4):2380-9. doi: 10.1074/jbc.M505986200

2005

Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays.

Costello C M, Mah N, Häsler R, Rosenstiel P, Waetzig G H, Hahn A, Lu T, Gurbuz Y, Nikolaus S, Albrecht M, Hampe J, Lucius R, Klöppel G, Eickhoff H, Lehrach H, Lengauer T, Schreiber S (2005); PLoS Med., 2(8):e199. doi: 10.1371/journal.pmed.0020199